In many fields of industry, e.g., chemical/pharmaceutical manufacturing, food processing, metallurgy/materials engineering, etc., it is often necessary to blend different ingredients to attain some desired mixture. It can be useful to monitor the properties of the mixture during blending to verify that the blending process is proceeding as planned. In some cases, it may be desirable to monitor changes in composition, phase, or other properties of the ingredients in the mixture, as can often occur where the mixture is reactive, or where it is heated or otherwise acted upon during blending. In other cases, it may simply be desirable to monitor the properties of the mixture during blending to confirm the degree of blending, i.e., whether the blend ingredients are mixed to the desired degree. Looking specifically to the field of pharmaceutical manufacturing as an example, active pharmaceutical ingredients (API) and excipients such as disintegrans, flow agents, binders, fillers and other ingredients are often blended before being tableted or filled into capsules. Each unit of the formulation, e.g., any single tablet or capsule, should contain a predetermined amount of API, and should dissolve at a predetermined rate, and reproducibly uniform and complete blending is needed to achieve this objective.
To control time and costs, it is desirable to cease blending as soon as mixing appears to be sufficiently thorough. Blending is a complex process because sometimes intensifiers need to be used to break up aggregates and sometimes it is necessary to limit the amount of mechanical energy imparted to the mixture. Ingredients are usually mixed in batches by tumbling or otherwise agitating them in a mixing bin, with the mixing bin having sufficient free space, and a suitable tumbling or agitation speed that the ingredients uniformly commingle over time as blending proceeds. Batch-type blenders using closed mixing bins having a variety of shapes are known, typically square bins, drum-like shapes or V-shapes, with ingredients typically being blended therein for a predetermined amount of time, or until a predetermined number of revolutions or oscillations are done. To facilitate emptying, the mixing bins typically have controls which cease bin motion when the bin is oriented such that an emptying port is situated at or near the bottom of the bin. The content of the bin can be examined by pulling samples from different depths through ports in the bin while the bin is stationary. Manufacturers often verify blending by sampling and testing a blend after a predetermined amount of blending has occurred, e.g., after a predetermined blending time, or after a predetermined number of rotations of a batch-type blender rotating at a predetermined rate. The blender is stopped and a sample is taken to a laboratory and examined using conventional analytical methods such as molecular spectroscopy, wherein the sample is illuminated, often with non-visible light such as light in the infrared region of the spectrum, and the light reflected by, transmitted through, and/or not absorbed by the specimen is then captured and analyzed to reveal information about the characteristics of the specimen. As an example, a specimen may be illuminated with near-infrared light having known intensity across a range of wavelengths, and the light from the specimen can then be captured for comparison to the illuminating light. Review of the captured spectra (i.e., light intensity vs. wavelength data) can then illustrate the wavelengths at which the illuminating light was absorbed by the specimen, which in turn can yield information about the chemical bonds present in the specimen, and thus its composition and other characteristics. Libraries of spectra obtained from reference specimens of known composition are available, and by matching measured spectra versus these reference spectra, one can then determine the composition of the specimens from which the measured spectra were obtained.
Periodic halting of the batch-type blender to collect and test samples is disadvantageous because it interrupts the blending process and increases the time needed for blending. It might be assumed that manufacturers could instead simply start blending ingredients, and later cease blending at some time in the future when complete blending might be presumed. However, this is not always the case. “Overblending” (i.e., blending for longer than needed) can sometimes lead to adverse effects since some mixture ingredients may initially disperse, but then undesirably re-aggregate over time.
Continuous blending systems are also used. These typically have an inlet, an outlet, and some means to mix the ingredients as they are transferred from the unblended state at the inlet to the blended state at the outlet. Samples can be collected, or the blend can otherwise be observed, at locations along the blender or at its outlet. Continuous blending systems are often unsuitable owing to the size/length of the blender needed to obtain the desired degree of mixing, the difficulty typically encountered with reconfiguring the blender to accommodate different blends, and/or owing to the aforementioned need to optimize mechanical energy input to the blend ingredients.
Attempts have been made to reduce the time and burden of blend testing in batch-type blenders. At-line methods, wherein the blender is stopped and a sample is analyzed in an instrument situated in close proximity to the blender, have been used to assess the degree of blending. Additionally, instruments have been modified for use directly on the blenders themselves. To illustrate, spectrometers (typically near-infrared and fluorescence spectrometers) have been built as portable modules and are detachably affixed to blenders' mixing bins. The blend ingredients are placed in a blender, and during blending, the ingredients tumble over an observation window in the mixing bin, covering the window when it is at or near the bottom of the rotating bin and uncovering it when it is at or near the top of the rotating bin. The spectrometer directs input light through the window and captures the spectra of output light scattered/reflected from the blend as it covers the window, with this light being characteristic of the blend's properties (more particularly, of the blend's average or bulk properties, as represented by the mixture resting across the area of the window from which the output light is captured). The spectrum changes as blending progresses, and the blend is assumed to be finished when the spectrum does not change any further. These types of “on-bin” devices have limited performance capabilities because of space and weight limitations for the blenders' mixing bins. Additionally, such “on-bin” devices typically require time-consuming pre-blending calibration, wherein known mixtures are analyzed prior to blending to establish datum points (e.g., reference spectra) for subsequent measurements.
A review of this type of analysis reveals that capturing one bulk spectrum per rotation of the blender provides insufficient analytical information about the degree of mixedness and the relative positions of the blend ingredients, and fails to recognize the conditions under which blend ingredients begin re-aggregating. There is significant interest in additional and improved arrangements for obtaining information regarding the distribution and uniformity of blend ingredients in a rapid and accurate manner which offers little or no interference to the blending process.